It has been reported that nutrient deprivation [31,32] and overfeeding [33,34], ketogenic and high carbohydrate diets [35,36], protein restriction [37,38,39], physical exercise [40,41,42], and other metabolic stresses, such as obesity, type 2 diabetes, or nonalcoholic fatty liver disease (NAFLD) [43], are capable of inducing FGF21 expression and/or signaling; and even more interesting, FGF21 metabolic effects will depend on the inducer factor or stress condition. The gene discussed is FGF21; the disease is obesity due to melanocortin 4 receptor deficiency.